Brain metastases occur in approximately 15% of breast cancer patients and confer a dismal prognosis. Brain metastases are thought to increasing as a sanctuary site, as systemic control of breast cancer metastases improves. We are conducting microarray analysis of surgically resected brain metastases of breast cancer, using laser capture microdissection, amplification and 30K cDNA arrays. These data are being compared to a cohort of unmatched primary breast tumors, matched for histopathology, TNM and grade.A heat map comparing gene expression differences between brain metastses and unmatched primary tumors has been complied and is undergoing validation via RT-PCR. Targets of translational interest include overexpression of Her-2, Hexokinase 2, histone deacetylases. Phenotypic work is commencing using a labeled cell line of MDA-MB-231 which will metastasize to brain in vivo. HDAC inhibitor treatment of the line is under investigation.